Amyloid deposits in the islets of Langerhans of the pancreas are a common finding in non-insulin-dependent diabetes mellitus. The main protein constituent of these deposits is a 37-amino acid peptide known as amylin that resembles calcitonin gene-related peptide, a neuropeptide. We have isolated cDNA clones corresponding to the rat amylin precursor from an islet cDNA library and we show that this peptide is encoded in a 0.9-kilobase mRNA that is translated to yield a 93-amino acid precursor. The amylin peptide is bordered by dibasic residues, suggesting that it is proteolyzed like calcitonin gene-related peptide. The peptide sequences flanking the amylin sequence do not resemble the calcitonin gene-related peptide flanking sequences. RNA hybridization studies show that amylin mRNA is abundant in the islets of Langerhans but is not present in the brain or seven other tissues examined. Dietary changes, such as fasting or fasting and refeeding, have little effect on amylin mRNA expression. This tissue specificity suggests that amylin is involved in specific signaling pathways related to islet function. levels and glucose-stimulated insulin secretion (13). Leighton and Cooper (14) found that CGRP inhibits insulin-stimulated glycogen synthesis in skeletal muscle, although it did not affect glycolysis. A comparable inhibition was observed using amylin purified from the pancreas of diabetic patients or synthetic amylin (14,15). No effect was seen in adipose tissue. These studies suggest that amylin may affect insulin secretion and the sensitivity of peripheral tissues to insulin.To define the primary structure of amylin in the islets, we have isolated and characterized cDNAs encoding rat amylin from an islet cDNA library.l Sequence analysis shows that a 0.9-kilobase mRNA encodes a 93-amino acid precursor that is proteolyzed to yield the final amylin product. RNA expression studies show that this molecule is expressed at high levels in the islets of Langerhans of normal animals but is not detected in the brain or any of seven other tissues in the rat. Amylin thus appears to be a normal constituent of the / cell that is processed in a fashion similar to other peptide hormones and is secreted with insulin from the islet.The pancreas ofpatients with non-insulin-dependent diabetes mellitus (NIDDM) contains deposits of amyloid, an extracellular protein matrix with unique staining characteristics (1-4). Small deposits of amyloid are also found in the pancreas of an elderly patient without diabetes; however, in patients with NIDDM they occur earlier and are more widespread. Cooper and coworkers (5, 6) and Westermark et al. (7,8) have purified and sequenced the peptide that is the major component of islet amyloid in NIDDM. This peptide, known as amylin, diabetes-associated peptide (DAP), or islet amyloid polypeptide (IAPP), is a 37-amino acid peptide that is 50% identical to calcitonin gene-related peptide (CGRP). Johnson et al. (9) have found amylin immunoreactive material in normal islets within insulin-containing s...
Although antibody inhibitors directed against blood coagulation factors are well known, antibody inhibitors directed against thrombin are rare. We describe three postsurgical patients with prosthetic cardiac valves who developed serum autoantibodies reactive with human and bovine thrombin, as demonstrated by coagulation studies and immunoblotting. Despite marked prolongation of the thrombin time in these patients, the inhibitors were not associated with significant clinical bleeding. The mechanism of antithrombin autoantibody formation following surgery in patients with prosthetic cardiac valves remains to be determined.
Amylin is a 37-amino acid peptide synthesized in the pancreatic beta-cell and cosecreted with insulin. In situ hybridization of nondiabetic rat pancreas shows that insulin and amylin RNA are both localized within the islet of Langerhans in a similar distribution. After 12 days of insulin-induced hypoglycemia (mean blood glucose 3.0 +/- 0.4 mM [54 +/- 8 mg/dl]), both insulin and amylin RNA fell greater than 95%. However, maintenance of euglycemia by simultaneous infusion of glucose with insulin did not suppress insulin or amylin RNA. Fasting suppressed amylin and insulin secretion from the isolated, perfused pancreas 70 and 58%, respectively, and with refeeding, secretion rates recovered to fed levels. Despite these changes in the rates of secretion, the relative ratio of amylin to insulin was not significantly different in fed, fasted, or refed rats. The molar ratio of insulin to amylin was estimated to be 100:2.3-2.6. Both insulin and amylin RNA was suppressed approximately 50% in response to fasting. Thus, although the absolute amounts of insulin and amylin change substantially under the conditions tested, the relative amounts of these peptides do not change.
Background: Postoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement. Methods: A multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations. Results: Consensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management. Conclusion: Salivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications.
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